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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Specific gastric inhibitory polypeptide (GIP) receptors were characterized in human benign insulinoma plasma membranes employing [mono-[125I]iodo-Tyr10]-GIP (125I-GIP) as the radioligand. GIP 1-42 inhibited 125I-GIP binding with an IC50 value of 10(-9) M. Scatchard analysis showed two classes of binding sites: a high-affinity site (Kd = 2.23 x 10(-10) M; Bmax = 24 fmol/mg protein) and a low-affinity site (Kd = 8.39 x 10(-9) M; Bmax = 118 fmol/mg protein). A synthetic replicate of human GIP 1-31 inhibited 125I-GIP binding with an IC50 value of 10(-8) M. The GIP binding sites of human insulinoma were coupled to adenylate cyclase stimulation. GIP 1-31 regulated the adenylate cyclase activity to the same extent as GIP 1-42. The concentrations of GIP required for maximal activity ranged from 10(-9) to 10(-8) M for either GIP 1-42 or GIP 1-31. The existence of functional GIP receptors in human insulinoma substantiates our recent reports demonstrating the presence of GIP binding sites in transplantable hamster insulinoma and indicates that GIP could exert a direct control of the beta-cell function in humans through a purely endocrine pathway.
Diabetes 1987 Nov
PMID:Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma. Binding of synthetic human GIP 1-31 and activation of adenylate cyclase. 282 18

We investigated the impact of blood glucose normalization on plasma levels of somatostatin-like immunoreactivity (SLI) in subjects with C-peptide-negative insulin-dependent diabetes mellitus (IDDM) and in totally pancreatectomized patients. Patients were studied during hyperglycemia and during normoglycemia, which was attained by Biostator-directed feedback insulin infusion. The experiments were performed in the fasted state and after a standardized breakfast. In IDDM (n = 6), basal levels of SLI were significantly higher than in nondiabetic subjects (n = 18). In IDDM, normalization of hyperglycemia was followed by a 40% decline in basal SLI (P less than .05). After the meal, SLI increased to the same absolute levels with or without feedback insulin treatment; however, the incremental response was 60% higher during feedback insulin treatment (P less than .05). Treatment also suppressed fasting and postprandial levels of glucagon, whereas gastric inhibitory polypeptide (GIP) levels were unaltered. In four pancreatectomized patients, normoglycemia tended to lower plasma levels of SLI by 50% (P less than .1). After breakfast, an SLI response was noted during normoglycemia, whereas no significant effect of the meal was seen during hyperglycemia. We conclude that in IDDM and in totally pancreatectomized patients, administration of insulin with subsequent normalization of blood glucose is accompanied by a decline in plasma levels of SLI in the fasted state, whereas the apparent response to a meal is enhanced. These effects on plasma levels of SLI probably reflect to a major extent release of somatostatin from the gastrointestinal tract.
Diabetes 1987 Jul
PMID:Basal and meal-induced somatostatin-like immunoreactivity in healthy subjects and in IDDM and totally pancreatectomized patients. Effects of acute blood glucose normalization. 288 57

In 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and secondary failure to sulfonylurea, a double-blind randomized study was performed comparing two regimes: insulin plus placebo (IP) and insulin plus glyburide (IG). The protocol included two hospitalization periods (days 1-18 and 78-85) and follow-up at the outpatient clinic for 325 days. The metabolic control was kept as tight as possible. The subjects underwent normoglycemic clamp studies and meal tests with determination of insulin, C-peptide, glucagon, somatostatin, and gastric inhibitory polypeptide in plasma. On IG, they demonstrated marked and long-lasting improvement of metabolic control: HbA1c decreased from 11.1 +/- 0.3% on day 3 to 8.3 +/- 0.4% (P less than .001) on day 78 and 9.1 +/- 0.5% (P less than .001) on day 325. In subjects on IP, the corresponding values were 10.3 +/- 0.5, 8.4 +/- 0.4 (P less than .001), and 8.9 +/- 0.5% (P less than .05). Body weight increased by 6.0 +/- 1.5 kg (P less than .005) on IG and 2.9 +/- 2.1 kg (NS) on IP. The daily insulin requirement decreased on IG from 62.5 +/- 12.9 U/day on day 7 to 33.5 +/- 8.8 U/day on day 83 and 34.6 +/- 8.9 U/day on day 325. On IP the insulin requirement was almost constant: 62.0 +/- 10.7 U/day on day 7, 55.5 +/- 7.7 U/day on day 83, and 54.7 +/- 7.9 U/day on day 325. Insulin sensitivity measured with the hyperinsulinemic clamp (plasma insulin approximately equal to 130 microU/ml) was similar on IP and IG at the initiation of the study and was unchanged on days 18 and 85. A key observation of this study, although the mechanism is unclear, is that isoglycemic-meal-related insulin requirement was diminished by insulin treatment, indicating improvement of meal-related insulin sensitivity. Glyburide increased basal and meal-but not glucagon-stimulated insulin and C-peptide levels, and also augmented the effect of meals on somatostatin release. We conclude that in NIDDM, IG regime promptly and continuously decreased insulin requirement and improved metabolic control. This effect is, at least during the first 3 mo, mainly due to enhanced insulin secretion. IG and IP treatment had no effect on insulin sensitivity during hyperinsulinemic-normoglycemic clamp, whereas meal-related insulin sensitivity was augmented.
Diabetes Care
PMID:Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea. 289 May 1

The effects of guar granules sprinkled over food on carbohydrate and lipid metabolism were studied in a double-blind cross-over trial in 18 patients with non-insulin-dependent diabetes mellitus (mean +/- SEM age 61.3 +/- 2.5 years). Five-gram guar granules (Guarem, Rybar Laboratories, Amersham, Bucks) were sprinkled over food at each main meal for 4 weeks, and during a 4-week placebo period (separated by a 2-week 'wash-out' period), 5 g wheat bran was taken in the same way. Diabetic treatment was not changed during the study. Mean fasting plasma glucose (FPG) concentration and glycosylated haemoglobin (HbA1) concentration after treatment were significantly lower than after the placebo period (FPG 8.29 +/- 0.47 vs 8.78 +/- 0.53 mmol/l, p less than 0.05; HbA1: 8.70 +/- 0.39 vs 9.09 +/- 0.39%, p less than 0.05). There was a 50% reduction in the incremental area under the postprandial glycaemic curve when guar was eaten with a standardized test meal. Total plasma cholesterol decreased from 5.79 +/- 0.29 to 5.19 +/- 0.22 mmol/l (p less than 0.05) after the guar treatment period. Guar ingestion reduced postprandial insulin and enteroglucagon responses, the latter significantly so, but had no apparent effect on gastric inhibitory polypeptide, pancreatic glucagon, gastrin, and pancreatic polypeptide.
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PMID:Guar sprinkled on food: effect on glycaemic control, plasma lipids and gut hormones in non-insulin dependent diabetic patients. 295 39

The post-prandial glucose and hormonal responses were followed in nine non-insulin-dependent diabetics after four randomized breakfast meals containing mainly wheat products. The effect of conventionally baked breads was compared with extruded crispbread-like products prepared from white or whole-grain wheat flour, respectively. The extruded whole-grain product gave significantly larger areas under the glucose and insulin curves than the corresponding baked bread, and resulted in higher C-peptide, gastric inhibitory polypeptide, and glucagon concentrations at certain time points. The mean incremental areas under the glucose curves were similar after white bread and the two extruded crispbread-like products. There were no significant differences between white and whole-grain bread. The results indicate that baked whole-grain wheat bread is to be preferred to corresponding extruded products in non-insulin-dependent diabetes mellitus.
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PMID:Hormonal and metabolic responses to breakfast meals in niddm: comparison of white and whole-grain wheat bread and corresponding extruded products. 299 Nov 71

Standardized breakfasts with or without beet-fibre were given, in random order, to non-insulin-dependent diabetics. The blood glucose levels were monitored continuously and hormonal responses were determined at regular intervals for 3 hr. After the beet-fibre breakfast including 10.8 g dietary fibre from the sugar beet, the glucose plateau level and the area below the curve were lower than after the control meal. The rate of glucose decrease was also slower after the beet-fibre meal. There were no notable differences with regard to the plasma levels of insulin, C-peptide or glucagon. The gastric inhibitory polypeptide response was greater during the first part of the curve, while the somatostatin response after the beet-fibre meal displayed a significantly larger total area below the curve. The results suggest that the diminished glycemic response after the beet-fibre meal is associated with an increased response of somatostatin, giving a reduced glucose absorption and a delayed gastrointestinal transit time.
Diabetes Res 1986 Feb
PMID:Reduced glycemic response to beet-fibre meal in non-insulin-dependent diabetics and its relation to plasma levels of pancreatic and gastrointestinal hormones. 300 77

The influence of L 364718 on islet responsiveness to sulfated cholecystokinin (CCK-8S) was investigated. In islets whose inositol-containing phospholipids were prelabeled during a 2-h incubation period, subsequent exposure to L 364718 (1 nM) significantly impaired the secretion of insulin usually noted in response to 200 nM CCK-8S in the simultaneous presence of 7 mM glucose. A higher level of the antagonist (10 nM) completely abolished insulin secretion. L 364718 (1-10 nM) reduced the efflux of 3H from myo-[2-3H]-inositol prelabeled islets in parallel with the reduction in secretion. L 364718 (10 nM) significantly reduced the accumulation of 3H-containing inositol phosphates usually noted with CCK-8S addition. L 364718, at levels 10- to 100-fold greater than those necessary to attenuate CCK-8S-induced insulin secretion, had no adverse effect on the insulin secretory response of freshly isolated islets to 10 mM glucose alone, 5 mM D-glyceraldehyde, 15 mM alpha-ketoisocaproate, or 50 ng/ml gastric inhibitory polypeptide. L 364718 (1000 nM) had no adverse influence on carbamylcholine (1 mM)-induced phosphoinositide hydrolysis. These results establish L 364718 as a potent and highly selective antagonist of cholecystokinin's stimulatory actions on beta-cells. Because of its potency, selectivity, and oral effectiveness, in vivo studies with L 364718, aimed at unraveling the pleiotropic effects of CCK-8S on glucose and insulin homeostasis, seem feasible.
Diabetes 1988 Oct
PMID:Stimulatory effects of cholecystokinin on isolated perifused islets inhibited by potent and specific antagonist L 364718 [corrected]. 304 73

To assess the contribution of changes in insulin secretion and clearance to the incretin effect (greater insulinemia after oral than after intravenous glucose), 10 healthy subjects were studied after oral glucose (1 g/kg body wt) and again when glucose was infused intravenously at rates to match arterialized plasma glucose concentrations after oral glucose. Although basal and integrated plasma glucose did not differ between oral and intravenous glucose, integrated responses of insulin (3.3 +/- 0.5 vs. 1.8 +/- 0.4 mU ml-1.240 min-1, P less than .001), C-peptide (456.5 +/- 58.5 vs. 327.9 +/- 46.3 ng.ml-1.240 min-1, P = .002), gastric inhibitory polypeptide, (16.8 +/- 3.5 vs. -2.8 +/- 1.0 micrograms.ml-1.240 min-1, P less than .001), and insulin secretion (6.6 +/- 1.1 vs. 4.7 +/- 0.7 U.240 min-1, P = .003) were greater with oral than intravenous glucose. However, insulin clearance, whether calculated as the molar ratio of integrated C-peptide to integrated insulin responses (6.9 +/- 0.7 vs. 14.2 +/- 3.8, P = .005) or from the formula insulin clearance equals insulin secretion divided by integrated insulin responses (1.1 +/- 0.2 vs. 2.5 +/- 0.7 L.min-1.m-2, respectively, P = .002), was less for oral than for intravenous glucose. Therefore, the incretin effect is mediated both by increased secretion and decreased clearance of insulin.
Diabetes 1988 Feb
PMID:Incretin effect due to increased secretion and decreased clearance of insulin in normal humans. 329 14

Diabetes, the most common metabolic disease, is responsible for the deaths of over 300,000 Americans annually. The incidence of the disease increases with age and since the U.S. population is graying, prevalence is also increasing. Obesity and family history are strong predictors of diabetes. The etiology of Type II diabetes is heterogeneous. The hyperglycemia of Type II diabetes can result from a variety of metabolic defects including impaired beta cell secretion, receptor deficiencies, or abnormal hepatic production or uptake of glucose. Other glucoregulatory hormones such as glucagon, growth hormone, cortisol, thyroid hormones, somatostatin, and gastric inhibitory polypeptide may contribute to the aberrations of carbohydrate metabolism. Environmental factors including stress, diet, and exercise may also contribute to the disease. Since most diabetics are obese, weight loss should be the first priority in improving status. A variety of diet and exercise regimens may help achieve this goal or even improve glucose control without weight loss. Due to the heterogeneity of the disease individualized treatment must be used to improve status of patients with the various metabolic defects of Type II diabetes.
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PMID:Dietary sugars and carbohydrate metabolism in type II diabetes. 330 10

Carbohydrate intolerance is positively correlated with animal fat consumption and is more common in beef eating populations. In contrast, individuals consuming diets comprised of polyunsaturated fats have a lower incidence of diabetes mellitus. To test the hypothesis that dietary fats may influence carbohydrate metabolism, serum glucose, insulin, and gastric inhibitory polypeptide (GIP) responses to three mixed test meals of varying fatty acid composition were assessed in 12 normal subjects. Fatty acids in the meals were either saturated fats or polyunsaturated fats derived from vegetables or fish. Each test meal provided 40% of a subject's calculated daily caloric requirement and contained approximately 45% carbohydrate, 40% fat, and 15% protein. Serum insulin responses were 62% higher (p less than 0.01) after the fish and 39% higher (p less than 0.01) after the vegetable meals compared to the saturated fat meal. No significant differences in insulin responses were observed between the vegetable and fish meals. Serum glucose concentration was slightly higher (p less than 0.02) during the fish meal than with the vegetable or saturated fat meals. The GIP levels were comparable following the fish and vegetable meals and were 25% lower than those observed with the saturated fat meal. These findings suggest that diets enriched with polyunsaturated fatty acids augment insulin secretion significantly more than a diet comprised primarily of saturated fatty acids. The mechanism for this increased insulin secretion is unknown but did not appear to be mediated through differences in serum glucose values or through the insulin-otrophic effects of GIP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polyunsaturated fatty acids augment insulin secretion. 332 Jan 56


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